Zytiga after failing nubeqa ?

[joeguy]

Has anyone had any luck with Zytiga after nubeqa fails to hold down PSA? I have been mCRPC for a few years now and Im curious if there is any chance Zytiga would work after the combination of Orgovyx/Nubeqa failed. I had some good results years ago when I was still nmCRPC with Firmagon/Xtandi, but had to stop due to toxicities. The orgovyx has been keeping my T level almost in single digits, so Im not sure how another testosterone lowering drug like Zytiga would change anything....... but Im willing to try it if its not a complete waste of time and money.

[Tall_Allen]

I think the PRESIDE trial opens up the possibility that using docetaxel along with a second second line hormonal may extend how long it works. In PRESIDE, enzalutamide first failed but was given a second life when combined with docetaxel. IMO, a different pair of hormonals may work as well or even better - just a guess, but it seems reasonable.

prostatecancer.news/2022/10...

[joeguy in reply to Tall_Allen]

thanks Allen ,

I don’t know about xtandi being reactivated after Docetaxel, but I know it had no effect on Nubeqa . I just finished Docetaxel last summer. I’m assuming that Nubeqa and Xtandi are very similar AR blocker type drugs, but Zytiga is more of a T lowering drug. My T is already very low fro Orgovyx, so I’m not sure what Zytiga would do differently…. But Im willing to give it a shot

[Tall_Allen in reply to joeguy]

Zytiga does a lot more than lower T. It prevents the adrenals from manufacturing a host of androgens, and it prevents cancer cells from manufacturing their own testosterone and from internalizing the androgen receptor (which makes it easier to activate).

[PCaWarrior]

Despite different mechanisms of action Zytiga and Xtandi share most resistance mechanisms. Nubeqa has different ones. Casodex appears to be a superset of Zytiga/Xtandi.

I think it is worth a try.

[PCaWarrior]

Orgovyx is a GnRH antagonist. It reduces T synthesized in the testes. This is most of your T. Some, though, is synthesized in the adrenals and the tumor itself.

Zytiga inhibits CYP17. It reduces T synthesis from the testes, adrenals, and the tumor.

Most of the T made in the tumor doesn't show up in serum T measurements.

[joeguy]

It will be interesting to see if there is any difference in a single digit testosterone level with orgovyx, and a single digit testosterone level with Zytiga with regard to PSA and tumor growth.

[MateoBeach]

Abiraterone +p may be worth a try. Consider the adaptive regimen of cycling it off and on if your PSA drops by 50% you stop it, then resume when PSA returns to baseline. Extends time to resistance for many.

A few cycles of standard BAT can restore sensitivity to ARSI drugs if you meet the criteria for it outside of a clinical trial. Sam Denmeade can consult review and advise.

Another consideration would be to get a PSMA PET scan now and see if you are a good fit for Plarify treatment.

[joeguy]

Hi Mateo

I am actually currently giving Pluvicto a shot with second dose coming up next week. PSMA scan showed wide spread PSMA avid bone and lymph node mets before the start of treatment, and PSA continues to rise (if that even means anything while on Pluvicto). I am intrigued by BAT, but I fear I would not be a good candidate because I have pain from bone mets.

[Toth]

I had better and longer-lasting lowering of PSA with nubeqa than with Zytiga. It varies widely from individual to individual apparently. Yinyin